title: 1,25(OH)2D3-mediated amelioration of aortic injury in streptozotocin-induced diabetic rats.
abstract: In this study, a single tail vein injection of streptozotocin (STZ)-induced rat model was employed to study the effects of 1,25(OH)2D3 supplementation, the active form of vitamin D, on diabetes-induced aortic injury. Aortas from different groups were assessed for histopathology, toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 expression by hematoxylin and eosin staining, immunohistochemistry staining, reverse transcription polymerase chain reaction, and Western blot analysis. High-dose 1,25(OH)2D3 (0.3 μg/kg/day) significantly prevented diabetes-induced aortic pathological changes and collagen deposition and decreased the expression of TLR4, MyD88, and NF-κB at both mRNA and protein levels in the aorta of STZ-induced diabetic rats (P < 0.01). In vitro studies in A7r5 cells (a rat embryonic thoracic aortic smooth muscle cell line) showed that high-dose glucose (25 mmol/L) enhanced TLR4 expression at both mRNA and protein levels by fourfold and twofold, respectively, at 24 h, which were significantly diminished by 1,25(OH)2D3 (1 × 10(-7) mol/L) by 50 and 36 %, respectively. Similar effects of high-dose 1,25(OH)2D3 on the expression of MyD88 were observed. Our results indicate that vitamin D has protective effects on diabetes-induced aortic injury and attenuates the expressions of TLR4, MyD88, and NF-κB in diabetic rats.
authors.affiliation: Department of Endocrinology, The General Hospital of Tianjin Medical University, Tianjin, 300052, China.
authors.forename: Fengao
authors.initials: F
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiuzi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shaofang
authors.initials: S
authors.lastname: Tang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.forename: Mingcai
authors.initials: M
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000293:injuries; D001018:Aortic Diseases / Q000188:drug therapy; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005947:Glucose / Q000494:pharmacology; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C498145:Rela protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014807:Vitamin D; D013311:Streptozocin; D003094:Collagen; D005947:Glucose